Covalent Coupling of Vitamin D3 to the Major Cat Allergen Fel d 1 Improves the Effects of Allergen-Specific Immunotherapy in a Mouse Model for Cat Allergy

Grundström, Jeanette; Neimert-Andersson, Theresa; Kemi, Cecilia; Nilsson, Ola; Saarne, Tiiu; Andersson, Matilda; Hage, Marianne van; Gafvelin, Guro

doi:10.1159/000327546

Cited by 30 publications

(30 citation statements)

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“…However, our findings are consistent with previous reports in mice showing the effects of SIT in the presence of calcitriol including the reduction of the Th2 cytokine IL-13 in the BALF (19,36). Because IL-13 expression is critical for the induction of AHR (38), the reduced IL-13 levels might at least partly explain the ameliorated AHR in D-SIT-treated mice.…”

Section: Discussionsupporting

confidence: 93%

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25-Hydroxvitamin D3 Promotes the Long-Term Effect of Specific Immunotherapy in a Murine Allergy Model

Heine

Tabeling

Hartmann

et al. 2014

The Journal of Immunology

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Calcitriol (1α,25-dihydroxyvitamin D3) is the active vitamin D metabolite and mediates immunological functions, which are relevant in allergy. Its therapeutic use is limited by hypercalcaemic toxicity. We have previously shown that the activation of the vitamin D receptor inhibits IgE production and that B cells can synthesize calcitriol from its precursor 25-hydroxyvitamin D3 (inactive precursor) [25(OH)D] upon antigenic stimulation. In this study, we address the impact of 25(OH)D on the development of type I sensitization and determine its role in allergen-specific immunotherapy. BALB/c mice were sensitized to OVA, under 25(OH)D-deficient or sufficient conditions. The humoral immune response over time was measured by ELISA. OVA-specific immunotherapy was established and studied in a murine model of allergic airway inflammation using lung histology, pulmonary cytokine expression analysis, and functional parameters in isolated and perfused mouse lungs. In 25(OH)D-deficient mice, OVA-specific IgE and IgG1 serum concentrations were increased compared with control mice. OVA-specific immunotherapy reduced the humoral immune reaction after OVA recall dose-dependently. Coadministration of 25(OH)D in the context of OVA-specific immunotherapy reduced the allergic airway inflammation and responsiveness upon OVA challenge. These findings were paralleled by reduced Th2 cytokine expression in the lungs. In conclusion, 25(OH)D deficiency promotes the development of type I sensitization and correction of its serum concentrations enhances the benefit of specific immunotherapy.

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Section: Discussionsupporting

confidence: 93%

“…In previous reports on murine models, SIT was started on days 2-14 after sensitization (in this study: day 21) and performed daily or alternating days (in this study: weekly intervals). Also, lung function analysis was determined 1-2 wk after SIT (19,36) and thus earlier than in this study (6 wk) (Fig. 3A).…”

Section: Discussionmentioning

confidence: 86%

25-Hydroxvitamin D3 Promotes the Long-Term Effect of Specific Immunotherapy in a Murine Allergy Model

Heine

Tabeling

Hartmann

et al. 2014

The Journal of Immunology

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“…It was also shown that the coupling to virus-like particles reduced the allergenic activity of the major cat allergen Fel d 1 [66]. Using Fel d 1 as a model allergen in a murine model of cat allergy, it was also demonstrated that covalent coupling of vitamin D3 to Fel d 1 improved the effects of SCIT [67].…”

Section: Cpg-conjugated and Other Coupled Allergensmentioning

confidence: 96%

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

Valenta

Campana

Marth

et al. 2012

Journal of Internal Medicine

101

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Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only diseasemodifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease.

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“…1,25-DihydrovitaminD3 has been shown to increase regulatory T-cell responses by affecting dendritic cells for their tolerogenic properties. In a mouse model for cat allergy, vaccine containing rFel d 1 covalently coupled to VitD3 was tested [46], showing superiority to rFel d 1 only.…”

Section: The Fusion Of Allergens To Immune Modifiers and Peptide Carrmentioning

confidence: 99%

Novel immunotherapy vaccine development

Jutel

Akdiş

2014

Current Opinion in Allergy &Amp; Clinical Immunology

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PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept -as well as large, multicenter clinical studies. RECENT FINDINGS: The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SUMMARY: The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients. Purpose of reviewAllergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-ofconcept -as well as large, multicenter clinical studies. Recent findingsThe most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SummaryThe cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

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Covalent Coupling of Vitamin D3 to the Major Cat Allergen Fel d 1 Improves the Effects of Allergen-Specific Immunotherapy in a Mouse Model for Cat Allergy

Cited by 30 publications

References 100 publications

25-Hydroxvitamin D3 Promotes the Long-Term Effect of Specific Immunotherapy in a Murine Allergy Model

25-Hydroxvitamin D3 Promotes the Long-Term Effect of Specific Immunotherapy in a Murine Allergy Model

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

Novel immunotherapy vaccine development

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